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Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination.

Fragile-X syndrome is a common form of mental retardation resulting from the inability to produce the fragile-X mental retardation protein. Qualitative examination of human brain autopsy material has shown that fragile-X patients exhibit abnormal dendritic spine lengths and shapes on parieto-occipital neocortical pyramidal cells. Similar quantitative results have been obtained in fragile-X knockout mice, that have been engineered to lack the fragile-X mental retardation protein. Dendritic spines on layer V pyramidal cells of human temporal and visual cortices stained using the Golgi-Kopsch method were investigated. Quantitative analysis of dendritic spine length, morphology, and number was carried out on patients with fragile-X syndrome and normal age-matched controls. Fragile-X patients exhibited significantly more long dendritic spines and fewer short dendritic spines than did control subjects in both temporal and visual cortical areas. Similarly, fragile-X patients exhibited significantly more dendritic spines with an immature morphology and fewer with a more mature type morphology in both cortical areas. In addition, fragile-X patients had a higher density of dendritic spines than did controls on distal segments of apical and basilar dendrites in both cortical areas. Long dendritic spines with immature morphologies and elevated spine numbers are characteristic of early development or a lack of sensory experience. The fact that these characteristics are found in fragile-X patients throughout multiple cortical areas may suggest a global failure of normal dendritic spine maturation and or pruning during development that persists throughout adulthood.

Adult↗

Spine loss and other dendritic abnormalities in epilepsy.

Studies of neurons from human epilepsy tissue and comparable animal models of focal epilepsy have consistently reported a marked decrease in dendritic spine density on hippocampal and neocortical pyramidal cells. Spine loss is often accompanied by focal varicose swellings or beading of dendritic segments. An ongoing excitotoxic injury of dendrites (dendrotoxicity), produced by excessive release of glutamate during seizures, is often assumed to produce these abnormalities. Indeed, application of glutamate receptor agonists to dendrites can produce both spine loss and beading. However, the cellular mechanisms underlying the two processes appear to be different. One recent study suggests NMDA-induced spine loss is produced by Ca2+-mediated alterations of the spine cytoskeleton. In contrast, dendritic beading is not dependent on extracellular Ca2+; instead, it appears to be produced by the movement of Na+ and Cl- intracellularly and an obligate movement of water to maintain osmolarity. A decrease in dendritic spine density was recently reported in a model of recurrent focal seizures in early life. Unlike results from other models, dendritic beading was not observed, and other signs of neuronal injury and death were absent. Thus, additional mechanisms to those of excitotoxicity may produce dendritic spine loss in epileptic tissue. A hypothesis is presented that spine loss can be a product of a partial deafferentation of pyramidal cells, resulting from an activity-dependent pruning of neuronal connectivity induced by recurring seizures. The dendritic abnormalities observed in epilepsy are commonly suggested to be a product and not a cause of epilepsy. However, anatomical remodeling may be accompanied by alterations in molecular expression and targeting of both voltage- and ligand-gated channels in dendrites. It is conceivable that such changes could contribute to the neuronal hyperexcitability of epilepsy.

Animals↗

N-methyl-D-aspartate receptor blockade inhibits estrogenic support of dendritic growth in a sexually dimorphic rat spinal nucleus.

The lumbar spinal cord of rats contains the sexually dimorphic, steroid-sensitive spinal nucleus of the bulbocavernosus (SNB). Dendritic development of SNB motoneurons requires the action of both androgens and estrogens. Estrogenic effects are limited to the initial growth of SNB dendrites through 4 weeks of age. During this postnatal period, dendritic growth in other spinal motoneurons is regulated by N-methyl-D-aspartate (NMDA) receptor activation. In this study, we tested whether NMDA receptor activation was involved in SNB dendritic growth and whether the estrogenic support of SNB dendritic growth was dependent on the activation of NMDA receptors. Motoneuron morphology was assessed in normal males, intact males treated daily with the NMDA receptor antagonist MK-801, castrated males treated with estradiol benzoate (EB), and castrated males treated with both EB and MK-801. SNB motoneurons were retrogradely labeled with cholera toxin-horseradish peroxidase at 4 weeks of age (when dendritic length is normally maximal) and reconstructed in three dimensions. Somal area and dendritic length of SNB motoneurons in MK-801-treated, intact males were below those of normal males. Dendritic growth was partially supported in EB-treated castrates, but this growth was blocked by MK-801 treatment. These results suggest that, as in other motoneurons, dendritic development in the SNB involves NMDA receptors and, furthermore, that the estrogen-sensitive component of SNB dendritic development requires their activation.

Animals↗

Intrinsic connectivity of the rat subiculum: I. Dendritic morphology and patterns of axonal arborization by pyramidal neurons.

The dendritic and axonal morphology of rat subicular neurons was studied in single cells labeled with Neurobiotin. Electrophysiological classification of cells as intrinsic burst firing or regular spiking neurons was correlated with morphologic patterns and cell locations. Every cell had dendritic branches that reached the outer molecular layer, with most cells having branches that reached the hippocampal fissure. All but two pyramidal cells had axon collaterals that entered the deep white matter (alveus). Branching patterns of apical dendrites varied as a function of the cell's soma location along the fissure-alveus axis of the cell layer. The first major dendritic branch point for most cells occurred at the superficial edge of the cell layer giving deep cells long primary apical dendrites and superficial cells short or absent primary apical dendrites. In contrast, basal dendritic arbors were similar across cells regardless of cell position. Apical and basal dendrites of all cells had numerous spines. Superficial and deep cells also differed in axonal collateralization. Deep cells (mostly intrinsically bursting [IB] class) had one or more ascending axon collaterals that typically remained within the region circumscribed by their apical dendrites. Superficial cells (mostly regular spiking [RS] class) tended to have axon collaterals that reached longer distances in the cell layer. Numerous varicosities and axonal extensions were present on axon collaterals in the cell layer and in the apical dendritic region, suggesting intrinsic connectivity. Axonal varicosities and extensions were found on axons that entered presubiculum, entorhinal cortex or CA1, supporting the notion that these were projection cells. Local collaterals were distinctly thinner than collaterals that would leave the subiculum, suggesting little or no myelin on local collaterals and some myelin on efferent fibers. We conclude that both IB and RS classes of subicular principal cells make synaptic contacts in and apical to the cell layer. Based on the patterns of axonal arborization, we suggest that subiculum has at least a crude columnar and laminar architecture, with ascending collaterals of deep cells forming columns and broader axonal arbors of superficial cells serving to distribute activity across multiple columns.

Animals↗

Dendritic orientation and laminar architecture in the rabbit auditory thalamus.

A laminar organization composed of the dendritic fields of principal neurons and afferent axonal arbors has been proposed as the anatomical substrate for the frequency map at several levels of the mammalian central auditory system, including the inferior colliculus and medial geniculate body (MGB). In contrast to the auditory thalamus in most mammals, the ventral division of the rabbit medial geniculate body (MGV) has cellular laminae visible in routine Nissl stains, allowing a direct comparison of the laminar organization with the dendritic architecture and frequency organization. In total 30 presumptive relay neurons in the MGV were labeled with the juxtacellular recording method, and their dendritic arbors were fully reconstructed from serial sections with the aid of a computer microscope. The spatial organization of MGV dendritic fields was analyzed using the dendritic prism, dendritic stick, and fan-in projection methods. Quantitative spatial analyses revealed that, for MGV neurons in the central pars lateralis subdivision, the major axis of the dendritic fields (approximately 29 degrees relative to the horizontal plane) was closely aligned with that of the Nissl laminae (approximately 25 degrees). Both were oriented orthogonally to the tonotopic axis. In contrast, cells in the pars ovoidea had their major axis of orientation parallel to the anteroposterior axis of the brain. Although a bitufted dendritic field was the norm, it was not uncommon for MGV neurons to have pronounced spatial asymmetries in their dendritic fields. A model is presented that incorporates cellular laminae and oriented dendritic growth to form frequency-related slabs within the MGV.

Animals↗

Polarized distribution of alpha5 integrin in dendrites of hippocampal and cortical neurons.

The distribution of immunoreactivity for the alpha5 subunit of the fibronectin receptor was evaluated in adult rat brain with particular interest in the cellular localization of immunostaining in the hippocampal formation and neocortex. Beyond localization to neuronal perikarya and short dendritic fragments within most brain areas, alpha5 immunoreactivity (-ir) was particularly dense within primary apical dendrites of pyramidal cells in both hippocampus and neocortex and within the dendritic arbors of cerebellar Purkinje cells. In hippocampal and cortical pyramidal cells, immunostaining was clearly polarized: alpha5-ir was not detectable in basal dendrites in hippocampal neurons and was limited to proximal arbors or absent from basal dendrites in pyramidal cells in superficial and deep layers of neocortex. Beyond this, alpha5-ir was distributed within the dendritic ramifications of the dentate gyrus granule cells and within perikarya and dendrites of occasional nonpyramidal neurons. Developmental studies demonstrated that, in both hippocampus and neocortex, alpha5-ir appears first within perikarya and is distributed to dendrites during the second postnatal week. These results are in accord with the broad hypothesis that integrins contribute to apical-basal differences in dendrites and that the integrin fibronectin (alpha5beta1) receptor, in particular, contributes to some late developing features of dendritic structure or function.

Animals↗

Age-related deterioration of pyramidal cell basal dendrites in rat auditory cortex.

The basal dendritic trees of layer V pyramidal cells in the rat auditory cortex were examined quantitatively in a group of 3-month-old and a group of 34- and 36-month-old rats. Two forms of analysis were used on the Golgi preparations: (1) the number of intersections between the basal dendrites and a series of concentric circles whose common center lies over the perikaryon center, and (2) the number of dendritic branches, by order, per neuron. The data indicate that in the old animals the density of the dendritic tree has decreased significantly within a radius of about 150mu of the perikaryon, yet the extent of the dendritic domain has not changed appreciably. Analysis of the dendritic branching suggests that there has been a deterioration not only in the peripheral branches of the dendritic tree, but also that entire dendrites have been lost. This loss of primary branches was confirmed through the reconstruction of layer V neuronal perikarya and their proximal dendrites from 1-mu plastic serial sections of auditory cortex. Concomitant with the loss of dendrites which accompanies advancing age is a tendency for the perikaryon to be smaller, but not distorted, in the old animals.

Aging↗

Golgi and EM studies of the formation of dendritic and axonal arbors: the interneurons of the substantia gelatinosa of Rolando in newborn kittens.

Golgi studies in newborn kittens show that the two most prevalent interneurons in Rexed's lamina II of the dorsal horn of the medulla, the stalked cell and islet cell (Gobel, '75a,b, '78b) form their dendritic arbors in a similar fashion. At birth, both cell types are present in forms ranging from immature, in which numerous short dendrites radiate from the cell body in all directions, to relatively mature in which their dendritic arbors have elongated in specific directions and the adult branching pattern is already evident. During postnatal maturation, many dendrites are lost while only a few go on to lengthen. The unmyelinated axons of both cells are first recognized in forms in which lengthening dendrites have taken on their preferred direction of orientation. The two parts of Rexed's lamina II, i.e., layers IIa and IIb have already reached their adult mediolateral width at birth and the neuropil has nearly achieved its adult compactness. Space in the compact neuropil for elongating neuronal and astrocytic processes becomes available through the disintegration of many existing dendrites and by an overall fourfold increase in the rostrocaudal length of the dorsal horn of the medulla during postnatal maturation. At birth, the lengthening of the plasma membranes of elongating neuronal and astrocytic processes proceeds as vesicles (addition vesicles) found in aggregates throughout dendrites, unmyelinated axons and astrocytic processes fuse with and become incorporated into the existing plasma membranes. In addition, many dendrites in layers IIa and IIb are beading up and disintegrating. Within the beads, neurotubules are lost and addition vesicles fuse with each other to form small cavities. These cavities continue to enlarge, hollowing out the beads. The cavities ultimately open to the intercellular space as their membranes fuse with the plasma membrane of the beads. Finally, the beads disintegrate and their plasma membranes fragment. The thread-like segments between adjacent disintegrating beads shrivel until they ultimately disappear. Disintegration of beaded dendrites results in very little debris and does not provoke a phagocytic glial reaction. The disintegration of a dendritic branch takes place in spite of synaptic input from non-primary axons and is thought to occur from a failure to establish synaptic connections with primary axonal endings.

Animals↗

Sprouting in the avian brainstem auditory pathway: dependence on dendritic integrity.

The brainstem auditory pathway of the chicken were used to examine the relationship between the maintenance of dendrites following denervation and the successful reinnervation (sprouting) by surviving afferents. In the system the third-order cells in n. laminaris receive spatially segregated binaural innervation from n. magnocellularis. Afferents from the ipsilateral n. magnocellularis innervate the dendrites on the dorsal aspect of n. laminaris cells, while afferents from contralateral magnocellular neurons innervate ventral dendrites via the crossed dorsal cochlear tract. Denervation of the ventral dendrites of n. laminaris cells by transection at the midline results in rapid and severe atrophy of the denervated dendrite. Unilateral cochlea removal induces transneuronal degeneration of 30-45% of the ipsilateral magnocellular cells, thereby partially denervating one dendrite of the n. laminaris cells on each side of the brain. In animals with long-standing transections of the crossed dorsal cochlear tract there is no evidence of sprouting the fibers from the ipsilateral n. magnocellularis when the projections of the surviving magnocellular neurons are traced with degeneration methods after a secondary cochlea removal. However, when dendrites of n. laminaris are partially denervated dendrites do not disappear. Furthermore, secondary lesions of the crossed dorsal cochlear tract or secondary cochlea removal reveal that these denervated dendrites are reinnervated by the afferents from the opposite n. magnocellularis which are normally restricted to the opposite dendrite of the n. laminaris cells.

Animals↗

Light and electron microscopic studies of the distribution of microtubule-associated protein 2 in rat brain: a difference between dendritic and axonal cytoskeletons.

A specific antiserum was used to ascertain the distribution of microtubule-associated protein 2 (MAP2) in the rat brain at the light and electron microscope levels. Light microscopy showed MAP2 to be present only in neurons, and only in the dendrites and the perikaryon of each cell. This same polarized distribution pattern was found in the Purkinje, Golgi, basket, stellate, and granule cells of the cerebellum, and also in neurons of the hippocampus, the olfactory bulb, and the midbrain. While labelling of the dendritic arborization was extensive and intense, MAP2 density tended to decrease in the proximal dendritic trunk. Particularly in large neurons (e.g., Purkinje, Golgi, and pyramidal cells), staining was reproducibly weaker in the cell body than in the main dendrites. Dendritic contours generally appeared smooth, without any evidence of staining of dendritic spines. An electron microscope examination of the cerebellum confirmed the presence of MAP2 reactivity in neurons and its absence from axons and non-neuronal cells. MAP2 in dendrites was associated with microtubules, while MAP2 in neuronal perikarya was associated with polyribosomes. There was no evidence of specific staining in dendritic spines and in postsynaptic densities. MAP2 is a novel dendritic marker and labels part of a specific dendritic cytoskeleton, different from that in axons and non-neuronal cells.

Animals↗

Ganglion cell dendritic structure and retinal topography in the rat.

The dendritic field size, the distribution of the dendrites relative to the cell body, and the overall shape of the dendritic field of type I ganglion cells in the rat retina were analyzed. These features of neuronal structure were related to the topography of the rat retina. As in the cat, the cell bodies of type I ganglion cells are arranged in a nonrandom mosaic. Previous work has demonstrated that the density of type I cells in the rat retina does not covary with the density of all ganglion cells. Type I dendritic field size varies over the retina; the increase in dendritic field size is accounted for better by the decrease in type I density than by the decrease in overall ganglion cell density. The center of the dendritic field of most type I cells is displaced in the plane of the retina from the cell body. Unlike in carnivore retina (Schall and Leventhal: J. Comp. Neurol. 257:149-159, '87), the dendritic fields in the rat are not displaced down the ganglion cell density gradient. Rather, there is a tendency for the dendritic trees, especially in temporal retina, to be displaced toward dorsal retina. Most of the dendritic fields are elongated, but the degree of elongation is less than that observed in carnivore or primate retina. Unlike in carnivore and primate retina (Leventhal and Schall: J. Comp. Neurol. 220:465-475, '83; Schall et al.: Brain Res. 368:18-23, '86), there is no relationship between dendritic tree orientation and position relative to any point on the retina in the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Golgi analyses of dendritic organization among denervated olfactory bulb granule cells.

In the vertebrate olfactory bulb, the primary projection neurons, mitral and tufted cells, have reciprocal dendrodendritic synapses with respective subpopulations of anaxonic interneurons called granule cells. In the neurological murine mutant Purkinje Cell Degeneration (PCD), all mitral cells are lost during early adulthood. As a consequence, a subpopulation of granule cells is deprived of both afferent input and efferent targets. The effect of this event on the morphology and sublaminar distribution of granule cells was studied with light microscopic Golgi procedures in affected homozygous recessive PCD mutants and normal heterozygous littermate controls. In the control mice, a minimum of three subpopulations were identified predominantly on the basis of the topology of apical dendrites and their spinous processes within the external plexiform layer (EPL) of the olfactory bulb: type I had dendrites extending across the full width of the EPL and a homogeneous distribution of spines; type II had dendritic arbors confined to the deeper EPL; type III had apical dendrites that arborized extensively within the superficial EPL with no arbors or spines present in the deeper EPL. Prior studies suggest that type II cells form connections with mitral cells; type III cells form connections with tufted cells; and type I cells may integrate information from both populations of projection neurons. In the mutant PCD mice, the classification of subpopulations of granule cells proved difficult due to a compression of dendritic arbors within the EPL. Dendritic processes followed a more horizontal tangent relative to the radial orientation seen in control mice. The length of dendritic branches was reduced by approximately 20% with a corresponding decrease in the number of spines. The density of spines (#/1 micron of dendrite) was constant in both controls and mutants at approximately 0.21. Truncation of the dendrites in the PCD mutants appeared to occur at terminal portions because the number of dendritic bifurcations was equal in both groups of mice. The data are discussed in terms of subpopulations of granule cells in the mouse olfactory bulb, the sublaminar organization of olfactory bulb circuits, and the capacity for survival and plasticity in the reciprocal dendrodendritic circuits mediated by the granule cell spines.

Animals↗

Dendritic morphology of pyramidal neurones of the visual cortex of the rat: I. Branching patterns.

The aim of this study was to provide quantitative descriptions of the branching patterns of basal and apical dendrites of pyramidal neurones from the visual cortex of the rat. Thirty-nine neurones from cortical layers 2/3 and 5, that had been injected with horseradish peroxidase, reconstructed, and measured with the light microscope as part of an earlier study (Larkman and Mason, '90; J. Neurosci. 10:1407-1414), were used. The cells had previously been divided into three classes, layer 2/3 cells and thick and slender layer 5 cells, on the basis of their dendritic morphology. The branching pattern of the basal and apical oblique dendrites was similar for all the cells. Between 3 and 9 basal trees arose from the soma and the number of tips in each tree varied widely, between 1 and 13. The path lengths of all the basal dendrites of a given cell were relatively constant, however. Most basal dendritic branching occurred close to the soma, such that terminal segments were much longer than intermediate segments and contributed approximately 90% of the total dendritic length of each tree. Terminal segments showed only a narrow range of diameters. Most apical oblique trees arose from the proximal part of the apical trunk. They tended to be less highly branched but were otherwise extremely similar to basal trees. Distal oblique trees were unbranched or branched only once, and their terminal segments tended to be shorter and thinner than those of basal trees. The branching pattern of the apical terminal arbors was different, with many longer intermediate segments. The terminal segments tended to be thinner than those of basal or proximal oblique trees. Slender layer 5 cells were without obvious terminal arbors. The basal and proximal oblique dendrites jointly sampled a roughly spherical volume of cortex centred about the soma, and together they accounted for the substantial majority of the cell's total dendritic shaft membrane area. Comparisons with previous studies suggest that intracellular HRP injection can yield a more complete visualization of dendritic morphology than is obtained using Golgi-based methods (unless cells are reconstructed across tissue slabs), and can therefore result in a different view of the relative importance of the various components that make up the cell's dendritic system.

Animals↗

Androgenic regulation of dendritic trees of motoneurons in the spinal nucleus of the bulbocavernosus: reconstruction after intracellular iontophoresis of horseradish peroxidase.

Androgen-sensitive motoneurons in the spinal nucleus of the bulbocavernosus (SNB) in adult male rats were labeled after intracellular iontophoresis of horseradish peroxidase, after which they were fully reconstructed in three dimensions in order to measure their dendritic trees. Three groups of rats were compared: intact adult male rats and male rats castrated as adults and given Silastic tube implants containing either testosterone or nothing. In the high-androgen groups (intact males and testosterone-treated castrates), soma size and the diameter of the first-order dendrites were larger than in blank-treated castrates. Moreover, the terminal dendrites in all groups possessed growth cones, implying that the dendrites of these motoneurons are capable of growth in adulthood. However, there were no statistically significant group differences in the length, membrane surface area, or volume of the dendritic trees, or in the orientation or branching symmetry of dendrites. In general, there were positive correlations between the size of the motoneuronal soma and various measures of the size of the dendritic tree and between the diameter of individual stem (first-order) dendritic branches and the size of remainder of that dendrite. These data suggest that there may be a modest effect of androgen on the size of the dendritic trees of SNB motoneurons in adulthood, although the effect is much smaller than has previously been reported.

Androgens↗

Relationships between dendritic morphology and cytochrome oxidase compartments in monkey striate cortex.

In primate striate cortex, staining for the mitochondrial enzyme cytochrome oxidase reveals a regular pattern of intense staining, the blobs, which are surrounded by the lighter stained interblob regions. Neurons in both compartments exhibit profound functional differences: blob cells have color selective, unoriented receptive fields, whereas interblob cells are usually not color selective and have oriented receptive fields. Neuroanatomical tracing studies have shown that blob and interblob cells receive different inputs and participate in different projections. It is not known, however, whether this compartmental organization is also reflected in the dendritic morphology of individual cells. We therefore combined intracellular staining with cytochrome oxidase histochemistry to study the relationship between cell morphology and blob pattern in layers 2 and 3 of macaque striate cortex. Single cells were injected with the fluorescent dye lucifer yellow in lightly fixed tangential sections. Adjacent sections were reacted for cytochrome oxidase to reveal the blobs. The spatial relationship between stained cells and the pattern of the blobs were subsequently determined by aligning the sections by using radially running blood vessels as landmarks. Our results show that pyramidal cells located in blob and interblob regions do not differ in their soma size, spine density, and basal dendritic field structure. This indicates that the characteristic functional properties of the neurons in both compartments do not depend on the morphology of their dendritic trees. Since the elongation of the dendritic fields of blob and interblob cells was also found to be similar, we conclude that cortical orientation selectivity is not generated through elongated dendritic fields. We found several cells with dendrites freely crossing the borders between blob and interblob regions. These cells might correspond to cells with "mixed" receptive field properties, e.g., color selective oriented cells, which in physiological studies were found at the transition from blob to interblob regions. However, there were also a number of cells that respected the borders. A quantitative analysis of the dendritic fields revealed that 67% of the cells located close to the borders have a tendency to confine their dendrites to only one compartment. Thus the pattern of basal dendrites of these cells might be shaped by the parcellation of the striate cortex in blob and interblob regions. These dendritic field asymmetries may help to maintain the segregation at the single cell level into different processing channels in monkey striate cortex.

Animals↗

Estrogenic support of motoneuron dendritic growth via the neuromuscular periphery in a sexually dimorphic motor system.

The lumbar spinal cord of rats contains the sexually dimorphic, steroid-sensitive spinal nucleus of the bulbocavernosus (SNB). In males, the growth of SNB dendrites is steroid-dependent: dendrites fail to grow after castration, but grow in castrates treated with androgens or estrogens. Blocking estradiol synthesis or estrogen receptors in gonadally intact males attenuates SNB dendritic growth, suggesting that estrogens are required and must be able to act at their receptors to support normal masculine dendritic growth. However, SNB motoneurons do not accumulate estrogens, suggesting that estrogens act indirectly to support SNB dendritic growth. In this experiment, we examined whether local estrogen action in the neuromuscular periphery was involved in the postnatal development of SNB motoneurons. Motoneuron morphology was assessed in gonadally intact and castrated males. Gonadally intact males were left untreated or given either blank or tamoxifen implants sutured to the target musculature, or tamoxifen interscapular implants. Castrated males were left untreated or were given estradiol by muscle or interscapular implants or systemic injection during the period of SNB dendritic growth. At postnatal day 28, when SNB dendritic length is normally maximal, SNB motoneurons were retrogradely labeled with cholera toxin-HRP and reconstructed in three dimensions. While interscapular tamoxifen implants were ineffective, blocking estrogen receptors at the target musculature resulted in attenuation of SNB dendritic growth. In contrast, while interscapular implants of estradiol were ineffective, local treatment with estradiol at the target musculature in castrated males resulted in masculinization of dendritic growth. Thus, estrogens may act by an indirect action in the neuromuscular periphery to support SNB dendritic growth.

Animals↗

Remodeling of retinal ganglion cell dendrites in the absence of action potential activity.

The dendrites of ganglion cells in the retina have an excess number of spines and branches that are normally lost during the first postnatal month of development. We investigated whether this dendritic remodeling can be prevented when the action potential activity of ganglion cells is abolished by chronic intraocular injections of tetrodotoxin (TTX) during the first 4 or 5 postnatal weeks in the cat. Dendritic tree morphologies of alpha and beta ganglion cells from TTX-treated, non-TTX-treated (contralateral eye), and normal control retinae were compared after intracellular filling with Lucifer yellow. Qualitative observations and quantitative measurements indicate that TTX treatment does not prevent the normally occurring loss of spines and dendritic branches. Indeed, the dendritic trees of both alpha and beta cells in TTX injected eyes actually have even fewer spines and branches than normal cells at equivalent ages. However, because the total dendritic lengths of these cells are also reduced after TTX blockade, spine density is indistinguishable from untreated animals at the same age. In addition, although dendritic field areas are not altered with treatment, the complexity of the dendritic trees is reduced. These observations suggest that dendritic remodeling can occur in the absence of ganglion cell action potential activity. Thus, the factors that influence the dendritic and axonal development of retinal ganglion cells must differ, because similar TTX treatment during the period of axonal remodeling does have profound effects on the final pattern of terminal arborizations.

Action Potentials↗

Alterations in the morphology of ganglion cell dendrites in the adult rat retina after optic nerve transection and grafting of peripheral nerve segments.

Transected ganglion cell axons from the adult retina are capable of reinnervating their central targets by growing into transplanted peripheral nerve (PN) segments. Injury of the optic nerve causes various metabolic and morphological changes in the retinal ganglion cell (RGC) perikarya and in the dendrites. The present work examined the dendritic trees of those ganglion cells surviving axotomy and of those whose served axons re-elongated in PN grafts to reach either the superior colliculus (SC), transplanted SC, or transplanted autologous thigh muscle. The elaboration of the dendritic trees was visualized by means of the strongly fluorescent carbocyanine dye DiI, which is taken up by axons and transported to the cell bodies and from there to the dendritic branches. Alternatively, retinofugal axons regrowing through PN grafts were anterogradely filled from the eye cup with rhodamine B-isothiocyanate. The transection of the optic nerve resulted in characteristic changes in the ganglion cell dendrites, particularly in the degeneration of most of the terminal and preterminal dendritic branches. This occurred within the first 1 to 2 weeks following axotomy. The different types of ganglion cells appear to vary in their sensitivity to axotomy, as reflected by a rapid degeneration of certain cell dendrites after severance of the optic nerve. The most vulnerable cells were those with small perikarya and small dendritic fields (type II), whereas larger cells with larger dendritic fields (type I and III) were slower to respond and less dramatically affected. Regrowth of the lesioned axons in peripheral nerve grafts and reconnection of the retina with various tissues did not result in a significant immediate recovery of ganglion cell dendrites, although it did prevent some axotomized cells from further progression toward posttraumatic cell death.

Animals↗